Allergic sensitization does not influence advancement or survival in oral cancer

A history of allergies has been said to be associated with a lower risk of head and neck cancer compared to the general population. However, it is not known whether having an allergic sensitization influences the prognosis and advancement of cancer disease. Thus, the aim of the study was to investigate the relationship between allergic sensitization and oral cancer advancement and patient survival. Allergen-specific IgE antibodies were investigated by ImmunoCAP™ Rapid in consecutive 80 patients with oral cancer. ImmunoCAP Rapid system tests a mix of representative inhalant allergens such as birch, timothy grass, mugwort, house dust mite, cat, dog, cockroach, olive (pollen), wall pellitory and mold. Eighty patients met the inclusion criteria for the study. Fifteen patients (19%) had positive ImmunoCAP test. There was no statistically significant difference in primary tumour size (T-stage) between groups (60% in allergy vs 68% in non-allergy had T1–T2 stage and 40% vs 32% T3–T4, respectively, p = 0.570). 27% of patients with allergy had nodal metastases compared with 37% of patients without allergy (p = 0.557). Both groups had comparable short-term survival. In conclusion, allergic sensitization does not seem to influence either the advancement or the short-term survival of patients with oral squamous cell carcinoma.

www.nature.com/scientificreports/detected were cat, dog, timothy, mold and house dust mite.The remaining 65 patients (81%) tested negative for presence of allergen specific IgE.
There was no significant difference in smoking history between groups.Smokers constituted 60% of nonallergy group compared to 40% of the allergy group (p < 0.160).The most common type of cancer in the cohort was tongue cancer, which was observed in 66% of the allergy patients and in 67% of the non-allergy individuals.

TNM staging in patients with allergy
To determine the influence of allergy on cancer advancement, we compared T-and N-stage of patients with and without allergy.There were no statistically significant differences in primary tumor size (T-stage) between groups (60% in allergy vs 68% in non-allergy had T1-T2 stage and 40% vs 32% T3-T4, respectively, p = 0.570).27% of patients with allergy had nodal metastases (N+) compared with 37% of patients without allergy (p = 0.557).No significant difference was observed in tumor-grading; 7% in allergy vs 11% patients in non-allergy had grade 1. 80% vs 57% had grade 2 and 13% vs 32%, respectively, presented with stage 3.

Overall survival (OS) in patients with allergy
The 3-year OS rate was 92% in allergy patients while 87% rate was observed for non-allergy patients (Fig. 1).There was no statistically significant difference in survival between the two groups (Log-rank test, p = 0.7334).

Use of antihistamines
The medical records of individuals who tested positive in the ImmunoCAP test were reviewed.It was found that among the 15 patients, 7 had a documented history of allergy in their medical records.Furthermore, 5 out of the 15 patients had been prescribed antihistamine medication and/or nasal steroids.

Discussion
To our knowledge, this is the first study looking into correlation between allergic sensitization and survival in patients with oral squamous cell carcinoma.Based on our cohort, patients with allergy had comparable prognosis as patients without allergy.Furthermore, we showed that having allergy does not seem to influence the advancement (TNM staging) of the disease.
Allergy is a complex disorder and its influence on cancer disease is difficult to establish.Different types of allergies and even different allergens can potentially have a distant influence on the risk of cancer development and advancement of the disease.In this project, we investigated patients with allergy to most-common airborne allergens in Swedish population such as: birch, timothy grass, mugwort, house dust mite (D. pteronyssinus), cat, dog, cockroach, olive (pollen), wall pellitory and mold (A.alternata).The prevalent symptoms of airborne allergies include sneezing, coughing, red and itchy eyes, swelling, or wheezing.Lindelöf et al. 10 looked previously into relationship between the risk of developing cancer and positive Phadiotop test in Swedish population.They did not find any correlation between having allergies and risk of cancer.Our study results extend their finding by showing that having allergy does not have a major impact on advancement of cancer and survival of patients with oral cancer.In our cohort, there was no statistically significant difference in size of the tumour or nodal advancement between patients with and without allergy.To our knowledge, this is the first report looking into this dependence in patients with oral squamous cell carcinoma.
In recently published studies, the main two theories have been discussed and proposed to justify the inverse association between allergies and cancer.According to the "immunosurveillance hypothesis", allergy is involved in the immune system's ability to recognize and eliminate tumour cells 11 .The second theory, the "prophylaxis hypothesis", suggests that allergy symptoms are the body's way of expelling potential carcinogens and pathogens.In this way, allergy plays a vital role in lowering the risk of cancer 11,12 .Previous studies suggest that IgE may have a natural immunological surveillance function in some malignancies 13 .Furthermore, IgE antibodies were shown to have a direct cytotoxic influence on malignant cells 11,14 .Ferastraoaru et al. in a recent review 15 emphasized that low or absent IgE levels may impede anti-tumor surveillance, as a correlation was observed between low IgE levels and a significantly higher risk of malignancy development.The role of IgE in anti-tumor immunity begins to be recognized; however, further studies are required to comprehensively understand its functions.
Several aforementioned studies showed lower risk of certain cancer types, including HNC, in populations with allergies compared to general population.A meta-analysis by Hsiao et al. indicated a statistically significant inverse association between head and neck cancer and allergies 9 .In particular, the association was clear for allergic rhinitis and was more pronounced among men.The inverse association favors the immune surveillance theory.However, no studies looking into the influence of allergy on prognosis or advancement of head and neck cancer have been performed.
A limitation of this study is that it is restricted to one center with a limited number of enrolled subjects.Furthermore, the follow-up time is short and does not allow analysis of the 5-year survival.Moreover, the methods employed did not include the measurement of specific IgE levels.Although IgE levels were not measured, we believe that the presence or absence of allergic sensitization can profoundly impact the immune system.Still, this is the first prospective study investigating the presence of IgE antibodies at the time of surgery in cancer patients.We plan also to follow up our patients to investigate the influence of allergy on long-term survival.Other potential confounding factors, which have not been analysed within the scope of this project, are the use of anti-allergy medication and total IgE level in the blood of enrolled patients.
In conclusion, based on our cohort, allergic sensitization does not seem to influence either the advancement or the survival of patients with oral squamous cell carcinoma.

Subjects
Eighty consecutive patients with oral squamous cell carcinoma who were willing to participate in the study and provided a written informed consent were enrolled.The age range was 23-91.Mean age equaled 65 years.There were 47 male patients (59%) and 33 female patients (31%).All patients underwent surgical excision of the primary tumour and sentinel node biopsy at Karolinska University Hospital, Stockholm, Sweden between December 2019 and September 2022.Patients provided two blood samples on the day of the surgery which were further analysed at the laboratory as described under.Eligible patients enrolled for this study met following inclusion criteria: (1) diagnosis of primary oral cancer squamous cell carcinoma (OSCC) (2) tumour excision with https://doi.org/10.1038/s41598-023-48879-8

Figure 1 .
Figure 1.Kaplan-Meier curve comparing of overall survival between patients with and without allergy.